Sepsis is a systemic inflammatory response syndrome (SIRS) associated with an infection, and is defined according to requirements for 4 items of: body temperature (being lower than 36° C., or higher than 38° C.); heart rate (being more than 90 times/min); respiration (respiratory rate being more than 20 times/min, or PaCO2 being less than 32 mmHg); and number of leukocytes (being no less than 12,000/mm3, or no greater than 4,000 mm3, or appearance of no less than 10% juvenile cells), that is, sepsis is considered to be positive when 2 or more items among these meet the requirements (see Nonpatent Document 1). In Nonpatent Document 1, seriousness of sepsis is defined according to bases subsequent to sepsis such as dysfunction of organs, lowering of blood flow, decrease in blood pressure, tissue circulatory disorder and the like. The seriousness is greater in the order of sepsis; severe sepsis; and septic shock, and the greater seriousness leads to multiple organ failure (MOF).
At present, fluid resuscitation, administration of an antibiotic, blood purification therapy, control of the blood glucose level, administration of corticosteroid or activated protein C, and the like are performed in treatment of sepsis. In addition, it is important to diagnose prognosis of patients who suffered from sepsis or sepsis-related multiple organ failure for deciding treatment principles hereafter. In particular, severe patients who must be admitted to an intensive care unit (ICU) are postulated to fall within any of entire stages from sepsis to multiple organ failure; therefore, a capability of determining a marker that correlates with final clinical outcome (i.e., survival or death) when admitted to the ICU is believed to be useful for selection of treatment strategy.
Conventionally, several blood markers have been reported to reflect the prognosis of sepsis. For example, Nonpatent Document 2 reports that there is a correlation between the content of IL-1 in blood and poor prognosis of a septic patient. However, there is also a report that is contrary to Nonpatent Document 2, and thus it has not been established as a prognostic diagnostic method. In addition, Nonpatent Document 3 reports that the content of IL-10 in blood is high in septic patients with poor prognosis, whereas it is significantly decreased in septic patients with favorable prognosis. However, an increase of IL-10 can be detected only 80% of septic shock patients; therefore, the detection is not satisfactory for a prognostic diagnostic method.
On the other hand, fatty acid binding proteins (FABPs) are a group of proteins having a molecular weight of about 15 kD, which are present in cytosol and have an ability of bind to fatty acids. Although FABP is believed to participate in regulation of metabolic enzyme systems by way of intracellular transfer or accumulation of fatty acids, details of their physiological function are unclear. At least seven molecular species have been known as FABPs such as liver-type (L-FABP), intestine-type (I-FABP), myocardium-type (H-FABP), brain-type (B-FABP), skin-type (C-FABP/E-FABP), adipocyte-type (aP2) and peripheral nerve cell-type (myelin P2), and their primary structures were determined. Any of these have a fatty acid binding capacity, and a region having a well conserved sequence can be fond in part. Taking into consideration these and other findings, they are believed to form a family evolved from a common ancestor gene; however, as a whole they have different structures with one another, and exhibit each specific tissue distribution. It should be noted that the designation such as liver-type or intestine-type means the tissue in which the FABP was initially found, and does not necessarily mean that the FABP is present only in the tissue.
Recently, it is reported that L-FABP included in the urine from septic shock patients significantly increases as compared with that in healthy individuals (see Nonpatent Document 4). In addition, Nonpatent Document 4 also reports that the urinary L-FABP level significantly decreases by carrying out a blood purification therapy (endotoxin adsorption: PMX) in the patients of the survival group among septic shock patients, whereas the urinary L-FABP level does not decrease in the patients of the death group; therefore, the urinary L-FABP can be a candidate of a marker for deciding an effect of blood purification therapy. However, the disclosure in this report is not practically applicable as a prognostic diagnostic method since there is a prerequisite of carrying out a blood purification therapy, and thus the prognosis cannot be diagnosed based merely on the of urinary L-FABP level.
Nonpatent Document 1: Crit. Care Med., 20: 864-874, 1992
Nonpatent Document 2: Thijs, L. G. and Hack, C. E., Inten. Care Med., 21: S258-263, 1995
Nonpatent Document 3: Van der Poll, J. Infect. Dis., 175: 118-122, 1997
Nonpatent Document 4: Abstract of the 24th Japanese Society for Apheresis (November, 2004) Session Number: 0-65